Adriamycin is a cytotoxic anthracycline antibiotic used in treatment of many types of cancer. Metformin is antidiabetic drug and is under investigation for treatment of cancer. The aim of this work was to study the effect of each of adriamycin and metformin alone and in combination on solid Ehrlich carcinoma (SEC) in mice. Eighty BALB/C mice were divided into four equal groups: SEC group, SEC + adriamycin, SEC + metformin, SEC + adriamycin + metformin. Tumor volume, survival rate, tissue catalase, tissue reduced glutathione, tissue malondialdehyde, tissue sphingosine kinase 1 activity, tissue caspase 3 activity and tissue tumor necrosis factor alpha were determined. A part of the tumor was examined for histopathological and immunohistochemical study. Adriamycin or metformin alone or in combination induced significant increase in the survival rate, tissue catalase, reduced glutathione and tissue caspase 3 activity with significant decrease in tumor volume, tissue malondialdehyde, tissue sphingosine kinase 1 activity and tumor necrosis factor alpha and alleviated the histopathological changes with significant increase in Trp53 expression and apoptotic index compared to SEC group. In conclusion, the combination of adriamycin and metformin had a better effect than each of these drugs alone against transplantable tumor model in mice.